Environmental and genetic factors play a role in the development of colorectal cancer. Heterocyclic aromatic amines (HAAs) in high-temperature cooked meat and cigarette smoke are potential human colorectal carcinogens. HAAs need to be metabolically activated before they exert their carcinogenic effects. Several enzymes that are encoded by cytochrome P4501A2 (CYP1A2), N-acetyltransferase 2 (NAT2) and possibly NAT1 are involved in this HAA activating pathway. Tea polyphenols are found to inhibit the formation of HAA adducts in animals, and therefore, may protect against the development of colorectal cancer in humans. The proposed study will utilize two established residential cohorts of Chinese to study the effects of dietary and non-dietary HAAs and green tea consumption on the risk of colorectal cancer. The Shanghai Cohort Study enrolled 18,244 men aged 45-64 years in Shanghai, China, during 1986-89. The Singapore Chinese Health Study enrolled 27,959 men and 35,298 women aged 45-74 years during 1993-1998. At recruitment, all cohort members provided detailed dietary and medical histories. Blood and urine specimens were collected from all Shanghai cohort members and about 50% of Singapore cohort members. The cohorts have been followed for the occurrence of cancer and death through routine ascertainment of new cases from the population-based Shanghai and Singapore cancer registries and vital statistical databases, and for the Shanghai Cohort Study, annual visits to all known surviving cohort members. To date, the cohorts have accumulated more than 680,000 person-years of observation. Among cohort members, 8,255 subjects have died and 5,735 have developed cancer, including 793 colorectal cancers. During the next 5 years, study investigators will assess the roles of dietary HAAs and tea polyphenol in the development of colorectal cancer using validated biomarker assays. The potential modifying effects of HAA activating genes and tea polyphenols on the HAA-colorectal cancer association will be explored. [unreadable] [unreadable]